TW200946678A - Aminosuger compound and production method thereof - Google Patents

Abstract

Disclosed is a compound useful as an active ingredient for a pharmaceutical composition having an a-amylase-inhibiting activity, particularly a pharmaceutical composition for the treatment of diabetes. Studies have been made for discovering a compound having an a-amylase-inhibiting activity among the compounds produced by Streptomyces sp. Strain 6982 which is a ray fungus belonging to the genus streptomyces, and it is confirmed that an aminosugar compound has an a-amylase-inhibiting activity. The aminosugar compound has an a-amylase-inhibiting activity, and therefore can be used as a prophylactic or therapeutic agent for diabetes, obesity, NASH (non-alcoholic steatohepatitis), particularly as an ameliorating agent for postprandial blood glucose elevation.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pharmaceutical composition, which is particularly suitable for use as an amino sugar compound which is an active ingredient of a pharmaceutical composition for sugar treatment. [Prior Art] Some of the polysaccharides taken from the diet will be digested by amylase from the saliva in the mouth and stomach H, and most will be digested by the alpha-amylase from the pancreas in the twelve and jejunum. Double sugar sugar. These substances are locally present on the epithelial chorion of the small intestine, and the glucosidase represented by carbohydrase and sucrase is hydrolyzed into a monosaccharide, which is absorbed by the intestinal tract alone. When the absorbed monosaccharide migrates to the blood to cause blood sugar to sputum, the pancreas secretes insulin, which reduces the release of glycogen from the liver, and also increases the sugar into the muscle and adipose tissue, causing the rising blood sugar to drop and keep the blood sugar constant. Sex. © However, in the case of diabetes, due to insufficient insulin secretion, insulin resistance (insufficient insulin action), and a state of chronic blood sugar control such as hyperglycemia when high blood is fasted after eating. In recent years, according to large-scale clinical trials, it has been confirmed that correction of hyperglycemia after eating is necessary in the development of diabetes mellitus and inhibition of diabetes progression. Evidence suggests that even a mild hyperglycemia after eating is an independent risk factor for heart disease death. Due to the background as described above, it is recognized that for postprandial hyperglycemia (for example, a state in which blood glucose is more than 200 mg/dL for 2 hours after eating), the importance of medical treatment and the necessity of intra-abdominal and oligosaccharide in urine The bud sugar rises again, or the sugar and sputum are the blood vessels that have been smashed to 200946678. Currently, the clinically used post-prandial hyperglycemia treatment is a glucosidase inhibitor of digestive enzyme inhibitors (such as Acarbose). And Voglibose). However, due to the inhibition of glucosidase, there are problems in causing side effects of gastrointestinal organ symptoms (abdominal swelling, diarrhea, soft stool, typhoid, fart, etc.).

Another type of post-nutrition hyperglycemia treatment (digestive enzyme inhibitor) may be an alpha-amylase inhibitor. When glucosidase is blocked, undigested oligosaccharides (disaccharides) are produced in large amounts, but since the amount of undigested oligosaccharides (disaccharides) is small, even if the α-amylase is inhibited, It is expected to cause symptoms of digestive organs such as diarrhea, but it can be blocked by sugar absorption. Several amino sugar compounds having amylase inhibitory activity have been reported so far. For example, it is reported that there is a trestatin derivative isolated from the genus Streptomyces sp. (the following formula, wherein η is 1 to 3) (Patent Document

And a malt oligosaccharide compound having a hexahydro-3,5,6-trihydroxy-1 fluorene-nitrogen heterocycle as an essential skeleton (Patent Document 2). 4 200946678 【化3】

(wherein η represents 〇~3, and X represents η or a hydrophobic group).

Further, in the following formula, a compound having a reducing sugar structure in which η is a terminal of 〇 to 3 is known (Non-Patent Document 1)

η OH

Acarviostatin IV 〇3 (n = Ref 3), which is disclosed in the non-patent document, has the formula C94Hi5 6N4 〇64, although it is the same as the compound of n=4 in the present application, but it is a compound having a reducing sugar structure at the end. It is structurally different. [PRIOR ART DOCUMENT] [Patent Document 1] JP-A-54-163511 [Patent Document 2] US Pat. No. 6,596,696 [Non-Patent Document] [Non-Patent Document 1] Carbohydrate Research, 343 ( 2008), 882-892 200946678 [Problem to be Solved by the Invention] The present invention provides a pharmaceutical composition which is particularly suitable for use as an active ingredient of a pharmaceutical composition for treating diabetes. [Means for Solving the Problem] Alpha-amylase hinders that the drug must have stability in the digestive tract. 0 Restlessness in the digestive tract represents the possible breakdown of the product, and causes undesired side effects. The inventors of the present invention have discovered a compound produced by Streptomyces sp. Streptomyces strain 6982 and have excellent ct-amylase inhibitory activity, and have been inspected for the purpose of exploring a pharmaceutical product.遂 to completion. That is, the present invention relates to a compound of the formula (I) or a salt thereof, a composition containing the compound of the formula (I) or a salt thereof, a compound containing the compound of the formula (I) or a salt thereof, and a pharmaceutical composition of 0 and an excipient And a method for producing a compound of the formula (I) or a salt thereof. 【化5】

-8 - 200946678 (wherein η represents 4, 5 or 6.) Further, the present invention relates to a microorganism which is cultured in a medium to produce a compound of the genus Streptomyces having a compound having an α-amylase inhibitory activity or a salt thereof, and The compound or a salt thereof is recovered from the culture solution, and a compound having an amylase inhibitory activity, a compound of the formula C94H156N4O64, C113H187N5O76 or c132H218N6o88 (except for a compound having a reducing sugar structure at the end) or a salt thereof, and the like or a compound thereof The composition of the salt. Further, the present invention relates to a pharmaceutical composition for preventing or treating diabetes comprising a compound of the formula (I) or a salt thereof, that is, a therapeutic agent for diabetes containing the compound of the formula (I) or a salt thereof. Further, the present invention relates to the use of a compound of the formula (I) or a salt thereof for the manufacture of a pharmaceutical composition for the prevention or treatment of diabetes, or the use of a compound of the formula (I) or a salt thereof for diabetes Prevention or treatment, and a method for preventing or treating diabetes, which comprises administering an effective amount of a compound of the formula (I) or a salt thereof to a patient. ❿ [Effects of the Invention] The compound of the formula (1) or a salt thereof has an α-amylase inhibitory action and can be used as a prophylactic or therapeutic agent for diabetes, obesity, and NASH (nonalcoholic steatohepatitis). Further, since it is different from the glucosidase inhibitor, it does not cause symptoms of digestive organs such as diarrhea, but it is expected to exhibit sugar absorption inhibition. In the compound (I) of the present invention, a compound wherein η is 4 is as follows. 200946678 【化6】

The compound of formula (1) is present as a geometric isomer. The compound of the formula (1) in the present specification describes only one form of the isomer. However, the present invention includes the isomers other than the isomer, and also includes the isomer separated, or a mixture thereof. The compound of formula (I) is present as an optical isomer based on an asymmetric carbon atom. The present invention is a separator comprising the optical isomer of the compound of formula (I), or a mixture thereof. The present invention further comprises a compound represented by the formula (I) which is pharmaceutically acceptable as a prodrug. The pharmaceutically acceptable pre-drug drug refers to a compound which can be converted into an amine group, a hydroxyl group or the like by decomposition with a solvent or under physiological conditions. The basis for the formation of the precursor drug can be, for example, Prog. Med., 5, 2 1 57-2 1 6 1 (1 985), and "Drug Development" (Guangchuan Bookstore, 1990), Volume 7, Molecular Design 163- The basis of 198. The salt of the compound of the formula (I) means a pharmaceutically acceptable salt of the compound of the formula (I), and sometimes an acid addition salt is formed. Specific examples thereof include inorganic acids such as hydrochloric acid, hydrogen bromide, hydrogen iodide, sulfuric acid, nitric acid, and phosphoric acid, and formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, and horses. Acid, lactic acid, malic acid, mandelic acid, tartaric acid, diphenylmethyl tartaric acid, p-methyl dimethoate tartaric acid, citric acid, methanesulfonic acid, ethylsulfonic acid, phenylsulfonic acid, p-tolylsulfonate Acid, aspartic acid, guanylamine, etc.-10-200946678 Acidic acid additional salt. The present invention further comprises various waters and solvents and materials of the compound of the formula (I) and salts thereof, and a crystalline polymorph. In addition, the invention also encompasses compounds which are characterized by various radioactive or non-radioactive isotopes. In the present specification, the "compound having a reducing sugar at the end" is not particularly limited, and examples thereof include Acarbose, Acarviostatin I03, Acarviostatin II03 'Acarvio statin El 03 'Acarvio statin IV Φ 〇3, and are free at the terminal end. A compound such as a natural substance of a monosaccharide of an aldehyde group (or a ketone group). (Production method) The compound of the present invention can be produced by using a microorganism belonging to the genus Streptomyces and having the ability to produce the compound or a pharmaceutically acceptable salt thereof. This microorganism is preferably Streptomyces sp. strain 6982 which is separated from the soil taken from the island of Iriomote in Okinawa Prefecture. The bacteriological properties of this strain are as follows. Streptomyces 6982 strain was isolated from soil samples taken from Iriomote Island, Okinawa Prefecture. The medium and method for investigating the morphology, culture traits, and physiological properties of the strain are mainly based on Shilling, Gottlieb (Shirling, EB and D. Gottlieb: Methods for characterization of Streptomyces species. I nt. J. S ys t. Bacteriol. 16,3 1 3-340,1 966), and Waksman (Waksman, SA: The actinomycetes V ο 1. 2: Classification, identification and description of genera and species: The -11 - 200946678

Williams and Wilkins Co., Baltimore, 1961). The culture temperature was 30 ° C, the number of culture cultivars was 14 days, and observation was made after the culture. The morphological observation was carried out by culturing on a yeast extract-starch agaric medium, and it was judged by observation with an optical or scanning electron microscope. The yeast extract-starch will contain 2.0g of powdered yeast extract S (made by Wako Pure Chemical Industries), l〇g soluble starch, and 16g of 1L aqueous solution of acacia, adjusted to pH=7_2 with 1M NaOH aqueous solution. It is then sterilized by autoclaving. The growth temperature is judged on the yeast extract-starch. The use of carbon sources is based on Pridoham-

Gottlieb's medium (Pridoham, TG and D. Gottlieb: The utilization of carbon compounds by some Actinomycetales as an acid for species determination: J. Bacteriol. .56: 1 07-1 1 4, 1 9 4 8 ) The bow I was used from "Methuen Handbook of Colour" (Kornerup, A. and JH Wanscher: Methuen Handbook of Colour, Methuen, London, 1 978). The analysis of the amino acid contained in the cell wall follows the method of Becker et al. (Becker, B., Μ. che. Lechevalier, RE Gordon and HA Lechevalier: Rapid differentiation between Nocardi a and Streptomyces by paper chromatography of whole-cell hydrolysates : Appl. Microbiol. 12,421-423, 1 964) ° The salt-based sequence of 16SrDNA is determined according to the method of Nakagawa et al. (Nakagawa Kyo, Chuan ▲崎 ▼ Haozi, classification and identification of Streptomyces PP. 83-117 In 2001, the Streptomyces Society of Japan edited: Tokyo, Japan Society Affairs-12-200946678 Center). The similarity search uses the FASTA search on the website of the National Institute of Genetics (a) http://www.ddbj.nig.ac.jp (b) DJ Lipman, WR Pearson: Rapid and sensitive protein similarity searches. Science, 227, 1 435- 1441 (1985), and

(c) WR Pearson, DJ Lipman: Improved tools for biological sequence comparison, Proc· Natl. Acad. S c i. USA, 85, 2444-2448 (1988) The 16S rDNA base sequence of the reference strain was purchased from National Genetics 硏Research database (http://www.ddbj.nig.ac.jp). The phylogenetic tree is made using the Clustal W kit software according to the adjacent polymerization method (Clustal W Thompson, J. D., Higgins DG, and Gibson, TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alighnment through sequence weighting, position- Specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673-4680, 1994) ° In addition, the similarity between DNA of Streptomyces strain 6982 and its neighboring strains can be determined by Jiangsaki et al. Confirm by method. (a) Ezaki, T., Hashimoto, Y., Takeuchi, T., Yamamoto, H., Liu, S. -L., Matsui, K & Yabuuchi, E., J Clin Microbiol., 26, (1 988) 1 708- 1 7 1 3 -13- 200946678

(b) Ezaki, T., Hashimoto, Y. & Yabuuchi, Ε·, Int J

Syst Bacteriol·, 39, (1 989) 224-229 In the present specification, the term "close relative strain" refers to a strain having the same 値 of 97% or more of the 16 SrDNA base sequence of Streptomyces sp. 6982 strain. Further, when it is known that the same enthalpy of the 16S rDNA salt base sequence is less than 97%, these are judged to be other species.

Stackebrandt, E. & Goebel, B. Μ., Int J Syst

Bacterid., 44, (1994) 846-849 (1) Morphological characteristics Nutritional hyphae are developed with irregular branches. The aerial hyphae are incompletely spiral, and more than 10 linked spores are formed on them. The spore surface is smooth and has an elliptical shape with a size of about 1.2x1.Ομιη. No sclerotia, sporangia, vegetative hyphae, and zoospores were observed. (2) Culture traits of aerial hyphae showed good on yeast extract - starch agar, yeast extract - malt extract, amaranth, amaranth, inorganic salt - starch, and glycerin - asparagus The birth of the tyrosine can be found on the tyrosine. The production of aerial hyphae was not found on peptone-yeast extract-ironwood. The color of aerial hyphae is grayish brown and brownish gray. The color of the inner surface of the growth is yellowish brown, brownish brown, grayish yellow, light yellow, brownish orange, and light orange. No melanin production was observed on the trypsin-yeast extract medium and the peptone_yeast extract-iron leaf. No soluble pigment production was found. The pigment in the bacteria does not change due to pH. This is shown in Table 1 for growth conditions on each medium. The shorthand representative -14- 200946678 has the following meaning. G: growth A: aerial hyphae R: color of the inner surface of the growth S: soluble pigment Table 1

Medium Growth Status Yeast Extract - Malt Extract Acacia G Good (ISP-2) A Rich, cottony, taupe (7E3) R Yellowish brown (5D6) S /frrr Mil: Oatmeal G Good ( ISP-3) A rich, cottony, brownish-brown (6E2) R brownish brown (6E3) S Λπτ I : V»,, inorganic salt - powdered amaranth G good (ISP-4) A rich, partial Brownish gray (6Ε2) R grayish yellow (4Β5) S te glycerol-asparagus yam G good (ISP-5) A rich, cottony, brownish gray (7E2) R light yellow (4A3) S and j\ \\ Peptone - Yeast Extract - Ironwood G Medium (ISP-6) A /rrr ^\\\ R Brownish Orange (5C6) S 4πτ 1111: Tyrosine Agar G Good (ISP-7 A light white R light orange (5A3) S ΒΕ ΒΕ (3) Cell wall type analysis After the complete cell decomposition product, the presence of LL-diamine oleic acid having amino acid can be confirmed. -15- 200946678 (4) Physiological properties for D-glucose, sucrose, D. xylose, D-fructose, L-rhamnose, raffinose, L-oligosaccharide, inositol, D•mannitol The utilization is positive. Table 2 shows the physiological characteristics of Streptomyces 69 82 strain. Table 2 __ Condition 1 characteristic growth brewing (. 〇12 ~ 45 optimal growth body (. 〇28 ~ 43 class melanin production - soluble pigment production for carbon source utilization D-glucose + + sucrose + D-dan + + D-fructose + L-rhamnose + raffinose + + L-gum yeast + + inositol + D-mannitol mellow + (5) According to 16SrDNA base sequence analysis, the 16SrDNA partial base sequence of Streptomyces 6982 strain is shown in Sequence sequence described later. Self-similarity search results, Streptomyces glaucescens DSM40716 strain (Accession No: X79 3 22) with similarity of 99.2% is the closest strain. In addition, Streptomyces albus NBRC of the reference strain of Streptomyces The similarity degree of 13014 strain (Accession No: AB 1 84257) was 96.2%. The phylogenetic tree made according to the sequence of 16SrDNA base-16-200946678 was formed in the same cluster with various streptomyces. (6) Identification Referring to the following documents (a) to (d), the strain is considered to be Streptomyces by morphological observation, chemical analysis, and 16SrDNA base sequence analysis. (a) Euzeby, JP List of Bacterial names with standing in Nomenclature: a folder available on the internet. Int. J. Syst. Bacteriol. 1 997, 47, pp.5 90-592. (b) Waksman, SA, et al.: The nomenclature and classification of the actinomycetes. Journal of Bacteriology, 1 943, 46, pp. 337-34 1. (c) Williams, S. T: Bergey's Manual of Systematic Bacteriology, Vol 4. 1 9 8 9. (d) Zhang, Z. et al.: A proposal To revive the genus © Kitastospora Int. J. Syst. Bacteriol., 1 997, 47, ρρ· 1048-1 054. The strain was named Streptomyces 6982. This strain is housed in the National Food Industry Research Institute and is registered under the registration number BCRC 91 0426 (registered on May 20, 2009). In addition, since the microorganism can be artificially or naturally mutated, the Streptomyces strain 6982 of the present invention includes, in addition to the naturally isolated microorganism, a person who artificially causes the mutation by ultraviolet rays, X-rays, chemical agents, and the like. Natural mutants. -17- 200946678 The amino sugar derivative of the present invention is a microorganism which can produce a compound having α-amylase activity by belonging to the genus Streptomyces, and more preferably a microorganism which can produce the amino sugar derivative, Further, it is more preferably 69 82 strains of Streptomyces, which are inoculated on a medium containing a nutrient source and then grown in an aerobic environment. The medium used for the culture may be a medium for growing microorganisms to be used, and a synthetic medium, a semi-synthetic medium or a natural (4) * ° ❹ nutrient may be used, and a nutrient source usable by the strain of the present invention may be used. For example, nitrogen sources may be soy flour, defatted soy flour, peptone, meat extract, corn steep liquor, cotton flour, peanut flour, soy flour, yeast extract, dried yeast, guanidine-amine, casein hydrolysate, fish meal Inorganic or organic nitrogen sources such as sodium nitrate and ammonium nitrate. The carbon source may use starch such as potato starch, corn starch, molasses, dextran, sucrose, glucose, maltose, trehalose, fructose, xylose, rhamnose, nectar, glycerin, etc. Starch and soy flour are preferred. d The metal salt may be added with a sulfate, a hydrochloride, a nitrate, a phosphate, a carbonate or the like of Na, strontium, Mg, Ca, Zn or Fe depending on the demand, and calcium carbonate and/or sodium chloride are preferred. Further, a known amino acid, methyl oleate, lard, cerium oxide, a surfactant, or the like can be suitably used depending on the demand to promote the formation of a compound or an antifoaming agent. In addition to this, it is also possible to use the production bacteria to make the use of the invention more useful. The culture method can be the same as in the case of generally producing an antibiotic, and the culture method can be solid culture or liquid culture. For liquid culture -18-200946678, any one of static culture, shock culture, and agitation culture may be carried out, but it is preferred to use aeration and agitation culture. The culture condition is that the culture temperature is such that the growth bacteria can grow to produce the temperature of the compound of the present invention, and can be applied within the range of 15 to 42 ° C, preferably about 20 to 30 ° C, 23 to 27 °. C is better. The pH can be applied to the range of 4 to 9, but it is preferably 6 to 8. The culture time varies depending on various conditions, and the general application range is 1 to 30 days, and 4 to 10 days is preferred. φ Regarding the separation of the target compound from the culture, a method of extraction, separation, and purification generally used in the separation from the microorganism metabolite can be suitably used. The substance present in the culture can be obtained by directly taking the culture solution, or by centrifugation, or by adding a filtration aid to the culture and then filtering. At this time, an organic solvent such as acetone, MeOH, EtOH or MeCN may be added to the culture solution, and hydrochloric acid or the like may be added to adjust the desired pH. Alternatively, the filtrate may be contacted with a suitable carrier to allow the production material in the filtrate to be adsorbed, and then the material may be separated by leaching with a suitable solvent. For example, the filtrate is brought into contact with a porous adsorption resin such as Amberlite (registered trademark) XAD2, Diaion (registered trademark) HP20, Diaion CHP20P, or Diaion SP8 50 to adsorb the substance. Next, the substance is eluted by using a mixture of an organic solvent such as acetone, MeOH, EtOH or MeCN and water. To adjust to the desired pH, hydrochloric acid or the like may also be added. At this time, the composition ratio of the substance can be efficiently obtained by gradually increasing the mixing ratio of the organic solvent from the low concentration stepwise or continuous to the high concentration. The compound of the present application is a compound which is not easily isolated in the form of a single product which is unstable to remove a reducing sugar compound, such as -19-200946678, and is purified by adding a base. In addition, in order to ensure the purity of the medicine, it was repeatedly purified. The compound of the formula (I) can be isolated and purified from a free compound, a salt thereof, a water and a substance, a solvent and a crystalline polymorph. The salt of the compound of the formula (I) can be produced by imparting a usual salt-forming reaction thereto. Separation and purification can be carried out by general chemical procedures such as extraction, crystal differentiation, and various color separation analysis. In the present specification, "purification" includes an operation for "separating" a compound of the present invention, and a compound of the present invention can be said to be "separated" as compared with the use of "purification". The various isomers can be produced by selecting an appropriate starting compound, or can be separated by utilizing the difference in physicochemical properties between the isomers. For example, optical isomers can be introduced by conventional optical segmentation of racemates (for example, by introducing crystals into non-mirrored stereoisomers with optically active bases or acids, and using card-type high performance liquid chromatography). The color layer analysis of the column and the like is obtained. In the present specification, "color layer analysis" means a color layer analysis generally used for chemical analysis, and is not particularly limited, and includes, for example, a gas chromatograph (GC), a liquid chromatography (LC), and a supercritical fluid. Chromatography (SFC), etc. In the present specification, the term "liquid chromatography (LC)" means a general term for a color layer analysis using a liquid as a mobile phase, and is not particularly limited, and includes, for example, a medium-speed liquid chromatography "high-speed liquid chromatography". Instrument (HPLC) and the like. The composition containing the compound of the formula (I) or a salt thereof means a composition obtained by purifying or isolating the compound of the formula (I), and it can also be used as a procedural precursor of the medicinal -20-200946678. . The compound is not particularly limited, and is, for example, one or more compounds of the formula (I) or a salt thereof, an active ingredient such as Acarviostatin IV 03, or a mixture thereof. Further, the present composition is not limited thereto, and it is preferable that the percentage of the area containing the compound of the formula (I) or a salt thereof is about 80% or more, preferably 85% or more, and 90% or more. For better, more than 95% are excellent, and 98% are the best. A pharmaceutical composition containing one or more of the compounds of the formula (I) or a salt thereof, which is an effective e component, can be used as an excipient which is generally used in the field, and a pharmaceutical excipient and The drug carrier or the like is prepared according to a general method of use. The administration system can be administered orally by a lozenge, a nine-dose, a capsule, a granule, a powder, a liquid, or the like, or an intra-articular, intravenous, intramuscular injection, a sitting agent, an eye drop, an eye ointment, A transdermal liquid preparation, an ointment, a transdermal patch, a mucosal solution, a mucosal patch, an inhalant, or the like, which is administered orally. © Lozenges, powders, granules, etc. can be used for the solid composition administered orally. In the solid composition, one or more active ingredients are combined with at least one of the less active excipients such as lactose, mannitol, glucose, hydroxypropylcellulose, microcrystalline cellulose. Mixing starch, polyvinylpyrrolidone and/or magnesium aluminosilicate. The composition may also contain a low activity additive such as a slip agent such as magnesium stearate, and a disintegrant such as sodium carboxymethyl starch, a stabilizer, and a dissolution aid, in accordance with a usual method. The lozenge or the nine doses may be coated with a sugar coating or a film of a gastric-soluble or enteric substance as needed. -21 · 200946678 The liquid composition for oral administration contains an opacifying agent, a solution, a suspension, a syrup or an elixir, which is generally acceptable for use, and contains a low-reactive diluent which is generally used, and is pure Water or EtOH. The liquid composition may contain, in addition to the low-reactive diluent, an auxiliary agent such as a melting agent, a wetting agent, a suspending agent, a sweetener, a flavoring agent, a fragrance, and a preservative. Injections for parenteral administration contain sterile aqueous or nonaqueous solutions, suspensions or opacifiers. The aqueous solvent contains, for example, distilled water for injection or physiological saline solution. The non-aqueous solvent contains, for example, propylene glycol, polyethylene glycol or a vegetable oil such as olive oil, an alcohol such as EtOH or a polysorbate 80 (the name of the party). These compositions may further contain an isotonic agent, a preservative, a wetting agent, an emulsifier, a dispersing agent, a stabilizer, and a dissolution aid. These were filtered by removing the virus filter, and sterilized by mixing a sterilizing agent or irradiating radiation. Alternatively, the aseptic solid compositions may be prepared and dissolved or suspended in sterile water or a sterile injectable vehicle prior to use. The external preparations include ointments, plasters, creams, gels, elixirs, sprays, lotions, eye drops, eye ointments and the like. It contains a commonly used ointment base, an emulsion base, an aqueous or non-aqueous liquid, a suspension or an emulsion. The ointment or emulsion base may, for example, be polyethylene glycol, propylene glycol, white petrolatum, white candied fruit, polyoxyethylene hardened castor oil, glyceryl stearate, stearyl alcohol, cetyl alcohol, polyglycerol, dehydrated sorbus Alcohol sesquioleic acid and the like. A solid, liquid or semi-solid form of a transmucosal agent such as an inhalant or a nasal spray can be produced by a conventionally known method. For example, an excipient known as -22-200946678, a pH adjuster 'preservative' surfactant, a slip agent, a stabilizer, a tackifier, and the like can be added as appropriate. Appropriate devices for inhalation or inhalation can be used for administration. For example, a compound or a spray device such as a metered spray device can be used, and the compound can be administered alone or in combination with a formulated mixture, or in combination with a pharmaceutically acceptable carrier to form a solution or suspension. A dry powder inhaler or the like may be used for single or multiple administrations, and a dry powder or a powder capsule may be used. Alternatively, a suitable expelling agent may be used, e.g., a type of gas gel spray which is pressurized with a suitable gas such as chlorofluoroalkane, hydrofluoroalkane or carbon dioxide. Generally, when administered orally, the dosage on the 1st is preferably about 0.01 to 100 mg/kg per kg of body weight, 0.1 to 10 mg/kg is appropriate, and it is administered once or twice to 4 times. versus. The mucosal agent is preferably about 0.001 to 100 mg/kg per kg of body weight, and is administered once a day to several times. The amount of administration needs to take into account the symptoms 'age, gender, etc., which are appropriately determined depending on various conditions. The compound of (I) can be used in combination with various therapeutic or prophylactic agents for diseases which exhibit an effective effect on the compound of the above formula (I). The combined use may be simultaneous, or may be administered continuously, or may be administered at desired intervals. The preparation to be administered at the same time may be a mixture or may be another preparation. [Embodiment] [Examples] Hereinafter, the production method of the compound of the formula (I) -23-200946678 will be described in more detail based on the examples. Further, the present invention is not limited to the compounds described in the following examples. The method for producing the compound of the formula (I) is not limited to the production method of the specific examples shown below, and the compound of the formula (I) can be produced according to the methods of the production, or by a method known to a related art. . The following shorthand notation will be used in this manual.

EtOH: ethanol

MeCN : acetonitrile

MeOH: methanol 0

NaCl: sodium chloride

NaOH: Sodium hydroxide TFA: Trifluoroacetic acid The following is explained in more detail by way of examples, but the present invention is not limited by these examples. Example 1 (Cultivation) The medium was a 100 mL Erlenmeyer flask containing 20 g of soluble starch, 1 g of Pinedex #3 (made by Matsutani Chemical Co., Ltd.), 20 g of soy flour, and 1 L of distilled water (pH = 7.0), which was dispensed in a flask of 30 mL each, and sterilized by autoclaving at 121 ° C for 30 minutes. The slant culture of Streptomyces strain 6982 was inoculated into the medium in a platinum inoculation loop, and shake culture was carried out at 30 ° C for 3 days. The production medium is taken from a triangular flask with a capacity of 100 mL and will contain -24- 200946678

100 g of soluble starch, 60 g of soy flour, 2.5 g of NaCl, 2 g of CaC03 and 1 L of distilled water (pH = 7.0), dispensed in a 30 mL portion of the flask, and then autoclaved at 121 ° C for 30 minutes. It is prepared by sterilization. In the production medium, the above-mentioned culture solution was inoculated with 2 mL of each flask, and shake culture was carried out for 7 days under 251. Crude purification from the culture solution φ The 22 L culture solution obtained by the above method was adjusted to pH = 3 with a 6 M aqueous HCl solution, followed by suction filtration. The filtrate was adjusted to 卩11=7 with a 6M aqueous solution of Na.sub.2, and then used to dissolve and eluted with a 25% aqueous solution of MeOH. This active image was washed with distilled water, 0.5 M, and 1 M NaCl aqueous solution using DOWEX 50W X1 (available from Dow Chemical Company) cation exchange resin (resin amount: 50 mL), and then eluted with 3 M NaCl aqueous solution. Next, using DaisoGel SP -1 20- 1 5/3 0-ODS-B (resin amount 1 L, manufactured by Daiso Co., Ltd.), by dissolving in 10%, 15% MeOH aqueous solution, respectively, obtaining Compounds A and B, and then 20% and 25%, respectively. The aqueous solution of MeOH was eluted to obtain Compound C. (1) Purification and separation of Compound A The active fraction of Compound A obtained by the above ODS column chromatography was used, and SP-1-20-1 5/3 0 was used. -ODS-B (resin amount 3 3 7 mL), dissolved in 2%, 3% MeOH aqueous solution (containing 0.05% TFA) -25- 200946678 After adjusting the activity to 6M Na〇H aqueous solution to pH=13, Diaion HP20SS (resin amount 500 mL) was used, followed by 12.5%, 15 ° / e MeOH aqueous solution (containing 〇. 〇 5 M NaOH) The activity was adjusted to pH = 7 with a 6 M aqueous HCl solution, and then eluted with a 50% MeOH aqueous solution using Diaion HP20 (resin amount: 200 mL). The dissolution zone was concentrated under reduced pressure, and then freeze-dried to obtain 1.14. g. The above powder of 200 mg dissolved in water was dissolved in a 2% MeCN aqueous solution (containing 0.05% TFA) using DaisoPcck SP-1 20-5-ODS-BP (20 x 250 mm, manufactured by Daiso Co., Ltd.). The active fraction was adjusted to pH==7 with a 6 M aqueous NaOH solution, and eluted with a 50% MeOH aqueous solution using Diaion HP20 (resin amount: 50 mL). The dissolution zone was concentrated under reduced pressure, and then freeze-dried to obtain 13 6 mg of a powder. The above powder dissolved in water was again dissolved using DaisoPcck SP-120-5-ODS-BP (20x250 mm) > in a 2% MeCN 7jc solution (containing 0.05% TFA). The activity was adjusted to pH with 6 M NaOH aqueous solution. = 7, Dissolution was carried out using Diaion HP20 (resin amount 30 mL) in 50% MeOH aqueous solution. The obtained active fractions were concentrated under reduced pressure, and then lyophilized to obtain Compound A (65 mg). (2) Purification and separation of Compound B was carried out by the above-mentioned 〇DS column chromatography to obtain a crude purification of 200946678 points, using SP - 1 20-1 5/30-ODS-B (resin amount 33 7 mL), dissolved in 3% to 7% aqueous MeOH solution (containing 0.05% TFA). After the activity was adjusted to pH = 13 with a 6 M aqueous NaOH solution, a solution of Diaion HP20SS (resin amount: 250 mL) was used, followed by elution with a 15%, 17.5%, 20% aqueous MeOH solution (containing 0.05 M NaOH). After the activity was adjusted to pH = 7 with a 6 M aqueous HCl solution, Diaion HP20 (resin amount: 50 mL) was used and eluted with a 50% aqueous MeOH solution. The dissolution zone was concentrated under reduced pressure, and then lyophilized to give 970 mg of powder. 4 50 mg of the above powder dissolved in water was eluted with DaisoPcck SP-120-5-ODS-BP (20 x 250 mm) in 2.2% aqueous solution of MeCN (containing 0.05% TFA). The active fraction was adjusted to pH = 7 with a 6 M aqueous NaOH solution, and then washed with a 50% MeOH aqueous solution using Diaion HP20 (resin amount: 115 mL). The dissolution zone was concentrated under reduced pressure, and then lyophilized to obtain 190 mg of Φ powder. The above powder dissolved in water was again dissolved using DaisoPcck SP-120-5-ODS-BP (20 x 250 mm) in a 2 · 2 % M e CN 7jc solution (containing 0.05% TFA). The active fraction was adjusted to pH = 7 with a 6 M aqueous NaOH solution, and then washed with a 50% MeOH aqueous solution using Diaion HP20 (resin amount: 30 mL). The obtained active fraction was concentrated under reduced pressure, and then lyophilized to give Compound B (129 mg). -27- 200946678 (3) Purification and separation of compound C The crude fraction obtained by the above-mentioned ODS column chromatography analysis was used, and SP-1 20-1 5/30-ODS-B (resin amount 80 mL) was used. It was dissolved in 2% aqueous MeOH (containing 〇.〇5% TFA). After the activity was adjusted to pH = 13 with a 6 M aqueous NaOH solution, Diaion HP20SS (resin amount: 200 mL) was used, followed by elution with 15%, 17.5%, 20% MeOH aqueous solution (containing 〇_〇 5 M NaOH). After the activity was adjusted to pH = 7 with a 6 M aqueous HCl solution, the mixture was eluted with a 50% MeOH aqueous solution using Diaion HP20 (resin amount: 150 mL). The dissolution zone was concentrated under reduced pressure, and then lyophilized to obtain lg powder. The above powder dissolved in water was eluted with DaisoPcck SP-120-5-ODS-BP (20 X 25 0 mm) in an aqueous solution of 2 · 2 % to 3.2 % M e CN (containing 0.05% TFA). The active fraction was adjusted to pH = 7 with a 6 M aqueous NaOH solution, and then washed with a 50% MeOH aqueous solution using Diaion HP20 (resin amount: 30 mL). The dissolution zone was concentrated under reduced pressure, and then lyophilized to obtain 2 36 mg of a powder. 184 mg of the above powder dissolved in water was again used for dissolution using DaisoPcck SP-120-5-ODS-BP (20 x 250 mm) in a 2.2% aqueous solution of MeCN (containing 0.05% TFA). The active fraction was adjusted to pH = 7 with a 6M aqueous NaOH solution, and then washed with a 50% MeOH aqueous solution using Diaion HP20 (resin amount: 30 mL). -28-200946678 The obtained active fractions were concentrated under reduced pressure, and then lyophilized to give Compound C (91 mg). Physicochemical properties of the compounds A, B and C The compounds A, B &C' after extraction, separation and purification described above have the following physicochemical properties.

(1) Compound A I) Color and shape: white powder CI 2) Acidic, neutral, basicity distinction: base property 3) Specific optical rotation: [a] 23D+157. (C = 0.5, H20) 4) Molecular formula: C94H156N4O64 5) High decomposition energy TOF-mass mass spectrometer: measured 値[M + 2H]2 + 1 1 83.4624 Theory 値[M + 2H]2+ 1 1 8 3.46 1 6 6 ) Alizarin analysis: C94Hi56N4〇64 14 H2O ' Calculated 値: C43.12, H7.08, N2.14 ❹ Measured 値: C43.27, H7.08, N2.05 7) Solubility: soluble in water, DMF, DMSO, but almost insoluble in acetonitrile, MeOH, EtOH, MeCN. 8) Ultraviolet absorption spectrum (solvent: water) ·· Display end absorption 9) Infrared absorption spectrum (v maJKBOcnT1) : 3 3 30,2925, 1655 , 1385 , 1150 , 1040 , 935 10) W-NMR spectrum (500MHz, D20): as shown in Figure 1. II) 13<: with 1^11 spectrum (1251^112, 020): as shown in Figure 2.

(2) Compound B -29- 200946678 υColor and shape: white powder 2) Acidic, neutral, and basic distinction: base property 3) Specific optical rotation: [a] 23D+153. (C = 0.5, H20) 4) Molecular formula: Cii3_Hi87N5〇76 5) High decomposition energy TOF-mass mass spectrometer: measured 値1416.0548 Theory 値[M + 2H]2+ 1 4 1 6.05 3 9 6) Alizarin analysis: Cii3H! 87N5〇76l6 H2O, Calculated 値: C43.50, H7.08, N2.24 Measured 値: C43.53, H7.09, N2.15 7) Solubility: soluble in water, DMF, DMSO, but almost nitrile , MeOH, EtOH, MeCN. 8) Ultraviolet absorption spectrum (solvent: water): shows end absorption i 9) Infrared absorption spectrum (v madKBOcnT1) : 3 3 65 1640 , 1385 , 1150 , 1045 , 935 10 ) 11141^11 spectrum (50014112, 020): Figure 3

11) 13C-NMR spectrum (125MHz, D20): as shown in Fig.. (3) Compound C 1) Color and shape: white powder 2) Acidic, neutral, basic difference: base 3) specific optical rotation :[a]23D+172° (C = 0.5,H20) 4) Molecular formula: Ci32H21gN6〇88 5) High resolution energy TOF-mass mass spectrometer: measured 値1648.6467 [M + 2H]2 ❹ insoluble in B, 2930, shown . ❹ Shown. [M + 2H]2 + -30- 200946678 Theory 値[M + 2H]2+ 1 64 8.6462 6) Elemental analysis: C132H218N6088 1 6 H20, Calculated 値: C44.22, H7.03, N2.34 値 Measurement: C44.23, H7.09, N2.35 7) Solubility: Soluble in water, DMF, DMSO, but almost insoluble in acetonitrile, MeOH, EtOH, MeCN. 8) Ultraviolet absorption spectrum (solvent: water): shows end absorption 0 9) Infrared absorption spectrum (V maJKBOcm·1) : 3 365, 2925, 1635, 1340, 1150, 1040, 935 10) 1H-NMR spectrum (500MHz , D20): as shown in Figure 5. 11) 13(: 4 PCT 11 spectrogram (125\11^, 020): as shown in Fig. 6. From the above physical and chemical properties, the chemical structures of the compounds A, B and C are determined as follows.

Wherein compound A: n = 4, B: n = 5, and C: n = 6. Further, when the compounds A, B, and C produced by the above method were analyzed by a high-speed liquid chromatography analyzer (HPLC) according to the following conditions, the area percentage (%) of the compounds A, B, and C was 99.0%, respectively. , 98.2%, 98.3%. The area percentage (%) is the sum of the waveform areas of the components obtained from the spectrum between 6 minutes and 22 minutes, and the ratio of the waveform area of each component is determined by -31 - 200946678. 1) Column: Unison US-C1 8 250-4.6mm (manufactured by Imtakt) 2) Mobile phase: 1-7% acetonitrile aqueous solution (containing 0.05% TFA) (0-20 minutes) 3) Flow rate: 1.0 ml/min 4) Detection: UV, 210nm

5) Column temperature: 50 ° C 6) Retention time: Compound A 16.3 minutes, Compound B 17.9 minutes, Compound C 19.2 minutes Reference 7) HPLC spectra of Compound A to Compound C are shown in Figure 9 to Figure 1 = 8) Chemical Handbook of Applied Chemistry, Sixth Edition (Nine Good), Chapter 8 Analysis and Measurement. Management, P 3 4 2~3 4 6 Example 2 The α-amylase inhibitory activity of the present invention is confirmed by the following method . (1) Experimental methods The pancreatic α-amylase solutions of mice, rats, dogs and monkeys were respectively obtained from ICR mice (male, 8 weeks old, purchased from Japanese SLC), SD rats (male '8 weeks old, Purchased from Charles River, Japan, the Miguel dog (male, 35 months old, purchased from the limited company N ARC), and the pancreas of the long-tailed macaque (male, 1 year old, purchased from 曰本 CLEA). The human saliva and pancreas &lt;2-killing enzyme solution was prepared by the enzyme from Sigma-Aldrich Co. -32-200946678. The α-amylase solutions were all prepared to be diluted to 800 U/mL using assay buffer (48 mM NaCl, 5.4 mM KCl, 28 mM Na 2 HP 4 , 43 mM NaH 2 P 4 , 3 5 mM mannitol, pH = 7.0). Various α-amylase solutions (20 U, 25 μM and a compound prepared by dissolving in assay buffer (25 μM were added to a 96-well plate and incubated at 37 ° C for 10 minutes. Thereafter, a starch solution (5 mg/) was added. mL, 50 μΙ〇 and then incubate at 37 ° C for 1 min. Add 0.33 M perchloric acid (50 μ! 〇 to stop the enzyme reaction, add 0.01 Μ iodine solution (50 pL) to make it color, and measure the absorbance (66 〇 Nm) Calculate the IC 5 〇値 concentration of the compound which inhibits the amylase activity of 50%. (2) Results The compounds of the present invention were found to have an inhibitory activity against α-amylase, and the compounds A, Β and C were observed. The inhibitory activity (IC5〇値) of mouse pancreatic α-amylase was 1.90ηΜ, 2.06 ηΜ and 1.73ηΜ, respectively, and the inhibitory activity (IC5〇値) of rat pancreatic α-amylase was ® 2 · 01ηΜ, 2.12 nM and 1.95nM, the inhibitory activity (IC5〇値) for canine pancreatic α-amylase was 2·06ηΜ, 2.38 ηΜ and 2·07ηΜ, respectively, and the blocking activity of monkey pancreatic a-amylase ( IC5〇値) are 2.14ηΜ, 1.90 nM and 2.02nM, respectively, for human saliva The inhibitory activities of α-amylase (IC5G値) were 2.20ηΜ, 1.87 ηΜ and 1·99ηΜ, respectively, and the inhibitory activities (IC5.値) for human pancreatic α-amylase were 2·02ηΜ, 2.11 ηΜ and 2·, respectively. 21. Example 3 -33- 200946678 The oral activity of the compound of the present invention was confirmed by the following method: (1) Experimental method Animals were male ICR (normal) mice (6 weeks old, purchased from Japanese SLC). The compound was prepared as a lysate with a 0.5% methylcellulose solution. Blood glucose sputum and plasma insulin sputum were measured for fasting mice for one night, and blood was collected by vehicle or compound A (0.3, 1, 3, 10 mg/kg). Oral administration was carried out, and oral administration was carried out immediately with carbohydrate (75 mg/mL starch, 25 mg/mL sucrose, 20 mL/kg), followed by plasma insulin sputum measurement at 0.25, 0.5 and 1 small @ hr. Blood collection was performed at 0.5, 1 and 2 hours after blood glucose measurement. Blood glucose was measured using glucose CII-TestWako (Wako Pure Chemical), and plasma insulin was administered with mouse insulin ELISA reagent group (Shibayagi Co., Ltd.) The measurement was performed separately. The test results are expressed as the mean standard deviation of the soil. The area under the blood glucose 値-time curve (AUC) based on the blood glucose 后 up to 2 hours after the administration of the compound, and the plasma of the plasma Q insulin sputum up to 1 hour are calculated. Insulin 値-time AUC, Dunnett's multiple range test was used to determine the drug-administered group and Compound A-administered group, and the risk rate was less than 5%. (2) Results The oral administration of Compound A (from 0.3 to 10 mg/kg) can be found to inhibit the increase in blood glucose, and the effect on the amount of 1 mg/kg or more is significant (Fig. 7). At this time, a dose-dependent and meaningful reduction in plasma insulin sputum was also found (Fig. 8). -34- 200946678 Example 4 The disaccharide hydrolase inhibitory activity of the compound of the invention was confirmed by the following method. (1) Test method Brush-like specimens made from small intestines of ICR mice, SD rats, Miguel dogs and long-tailed macaques, human small intestinal microsome specimens (BD 〇Bi(}Sciences; Lot 36869) as Various disaccharide hydrolyzed enzyme solutions, all of which were prepared using phosphate buffer (48 mM NaCl &gt; 5.4 mM KC1 &gt; 28 mM Na2HP04 1 43 mM NaH2P04, 35 mM mannitol, pH = 6.0). Evaluation of the disaccharide hydrolase inhibitory activity of mice, rats, dogs and monkeys: the disaccharide hydrolase solution (10 mg/mL, 40 μΙ^) and the compound solution (20 μΙ〇 added to the 96-well plate, Incubate for 10 minutes at 37 ° C. Thereafter, a disaccharide hydrolyzing enzyme substrate (sucrose enzyme: 100 mM sucrose, © maltase: 100 mM maltose, isomaltase: 100 mM isomalt, lactase: 1 mM lactose, Trehalase · lOOmM trehalose, 40 μM, and incubated at 37 ° C for 30 minutes. Add 0.0 4 M perchloric acid solution (100 μΙ〇 to stop the reaction, and then centrifuge (2,000 rpm, 15 minutes). Use glucose CII-TestWako reagent The concentration of glucose in the supernatant was determined by the pure drug. The disaccharide hydrolase inhibitory activity was calculated based on the enzyme (〇°/.) and the unadded compound (100%). Human disaccharide hydrolase inhibitor activity evaluation: The disaccharide hydrolase solution (0.1 mg/mL, 20 μM and the compound solution (ι〇μ[) was added to the 96-35-200946678 well plate and incubated at 37 ° C for 10 minutes. Thereafter, the double was added. Carbohydrase substrate (sucrose: l mM sucrose, maltase: 100 mM maltose, isomaltase: 100 mM isomalt, lactase: lOOmM lactose, trehalase: lOOmM trehalose, 20 μΙ〇, then at 37 ° Incubate for 30 minutes under C. Add 0.04 Μ perchloric acid solution (1 〇〇μΙ〇 to stop the reaction, centrifuge (2,000 rpm, 15 minutes), and measure the supernatant using glucose CII-TestWako reagent (Wako Pure Chemical) Glucose concentration in the solution. The double q saccharide hydrolase inhibitory activity was calculated based on the enzyme (〇%) and the unadded compound (100%). (2) Results The compounds of the present invention were found to be non-disaccharide after review. Water The enzyme (sucrose, maltase, isomaltase, lactase, trehalase) showed an inhibitory effect (IC5〇&gt; ΙΟμΜ). From the above test results, it was confirmed that the compound of the formula (I) has α-amylase inhibitory activity. And the effect of lowering blood glucose and plasma insulin sputum, and confirming that it can be used for the treatment of diabetes and the like. © [Industrial Applicability] The compound of the formula (I) or a salt thereof has an α-amylase inhibitory action, and can be used as a preventive or therapeutic agent for diabetes, obesity, NASH (nonalcoholic steatohepatitis) or the like. Further, unlike the glucosidase inhibitor, it is expected to prevent the absorption of sugar without causing symptoms of digestive organs such as diarrhea. [Free description of the sequence listing] -36- 200946678 The 16SrDNA partial base sequence of Streptomyces strain 6982 is shown in the sequence Table 0 [Simplified description of the drawing] [Fig. 1] 1H-NMR spectrum chart of Compound A. [Fig. 2] 13C-NMR spectrum chart of Compound a. Fig. 3 is a 1H-NMR spectrum chart of Compound B. ❹ [Fig. 4] &quot;C-NMR spectrum of compound b. Fig. 5 is a 1H-NMR spectrum chart of the compound c. Fig. 6 is a 13C-NMR spectrum chart of the compound c. [Fig. 7] The effect of Compound A on the inhibition of blood sugar rise when the carbohydrate is loaded. (A) is the change over time of blood glucose, and (B) is ACU (area under the blood glucose level - time curve). [Fig. 8] Inhibition of insulin uptake by Compound a when loading carbohydrates. (A) is the change over time of insulin sputum, and (B) is ACU (area under the concentration of plasma pancreatic Φ island blood in the blood-time curve). [Fig. 9] A chromatogram of HPLC chromatogram analysis of Compound A. [Fig. 10] A chromatogram of HPLC chromatogram analysis of Compound B. [Fig. 1 1] HPLC chromatogram of Compound C. -37- 200946678 Sequence Listing ❹ &lt;110&gt; Astellas Pharmaceuticals has a thief &lt;120> amino sugar compound and its production method &lt;130> A09004 &lt;150> JP 2008-102983 &lt;151〉 2008 -4-11 &lt;160&gt; 1 &lt;210> 1 <211> 1448 &lt;212> DNA &lt;213> Streptomyces &lt;400&gt; 1 cttaacacat gcaagtcgaa cgatgaacca cttcggtggg gattagtggc gaacgggtga gtaacacgtg ggcaatctgc cctgcactct gggacaagcc ctggaaacgg ggtctaatac cggatactga tcatcttggg catccttgat gatcgaaagc tccggcggtg caggatgagc ccgcggccta tcagcttgtt ggtgaggtaa cggctcacca aggcgacgac gggtagccgg cctgagaggg cgaccggcca cactgggact gagacacggc ccagactcct acgggaggca gcagtgggga atattgcaca atgggcgcaa gcctgatgca gcgacgccgc gtgagggatg acggccttcg ggttgtaaac ctctttcagc agggaagaag cgaaagtgac ggtacctgca gaagaagcgc cggctaacta cgtgccagca gccgcggtaa tacgtagggc gcaagcgttg tccggaatta ttgggcgtaa agagctcgta ggcggcttgt cgcgtcggat gtgaaagccc ggggcttaac cccgggtctg cattcgatac gggcaggcta gagttcggta ggggagatcg gaattcctgg tgtagcggtg aaatgcgcag atatcaggag gaa caccggt ggcgaaggcg gatctctggg ccgatactga cgctgaggag cgaaagcgtg gggagcgaac aggattagat accctggtag tccacgccgt aaacggtggg cactaggtgt gggcaacatt ccacgttgtc cgtgccgcag ctaacgcatt aagtgccccg cctggggagt acggccgcaa ggctaaaact caaaggaatt gacgggggcc cgcacaagcg gcggagcatg tggcttaatt cgacgcaacg cgaagaacct taccaaggct tgacatacac cggaaacact cagagatggg tgcccccttg tggtcggtgt acaggtggtg catggctgtc gtcagctcgt gtcgtgagat gttgggttaa gtcccgcaac gagcgcaacc cttgtcccgt gttgccagca ggcccttgtg gtgctgggga ctcacgggag accgccgggg tcaactcgga ggaaggtggg gacgacgtca agtcatcatg ccccttatgt cttgggctgc acacgtgcta caatggccgg tacaatgagc tgcgataccg cgaggtggag cgaatctcaa aaagccggtc tcagttcgga ttggggtctg caactcgacc ccatgaagtc ggagtcgcta gtaatcgcag atcagcattg ctgcggtgaa tacgttcccg ggccttgtac acaccgcccg tcacgtcacg aaagtcggta acacccgaag ccggtggccc 60 120 180 240 300 360 420 480 540 600 660 720 780 840 900 960 1020 1080 1140 1200 1260 1320 1380 200946678 1440 1448 Aaccccttgt gggagggagc tgtcgaaggt gggactggcg attgggacga agtcgtaaca aggta Gcc

❹ -2-

Claims (1)

200946678 VII. Application for patents 1 A compound or a salt thereof is represented by the formula (1) (wherein n is 4 to 6) [Chemical 1] ❹ , a compound or a salt thereof, which is cultured in a medium to produce a compound of the genus Streptomyces having a sputum:-amylase inhibitory activity or a salt thereof, and recovering the compound from the culture solution or As the salt, a compound having an α-amylase inhibitory activity and having a molecular formula of C94Hl56N4〇64, Cii3H187N5076, or C132H218N6〇88 (but a compound having a reducing sugar structure at the terminal) or a salt thereof can be obtained. 3. The compound of claim 2 or a salt thereof, wherein the microorganism of the genus Streptomyces sp. strain 6982 (BCRC 91 0426), the compound (but removed from the compound having a reducing sugar structure at the terminal) or a salt thereof. 4. A microorganism which is a Streptomyces sp. strain of the genus Streptomyces, BSER 91 0426, Streptomyces sp. 6982 strain, and a variant thereof. A composition comprising a compound of the formula (I) or a salt thereof, which is purified or isolated from a culture solution of a microorganism of the genus Streptomyces. 6- The composition of claim 5, wherein Streptomyces sp. 200946678 is a strain of Streptomyces sp. 6982 (BCRC 9104 26). A composition characterized by a color layer analysis comprising a compound of the formula (I) or a salt thereof in an area percentage of about 80% or more. 8. The composition of claim 5, wherein the compound or the phosphonium salt of the formula (I) having an area percentage of about 80% or more is contained according to the chromatographic analysis. 〆, ΠΠ- 9. The composition of claim 6 of the patent application, wherein the compound containing the formula (I) or the salt thereof is contained in an amount of about 80% or more based on the chromatographic analysis. A method for producing a compound or a salt thereof, which comprises culturing a Streptomyces microorganism capable of producing a compound having an amylase inhibitory activity in a medium, and recovering the compound from the culture solution, which is inhibited by a powdery enzyme A compound of the formula 'C94H156N4O64, c113H187N5o76, or c132h218n6088 2 (removed at a terminal having a reducing sugar structure) or a salt thereof. 11. The production method of claim 10, wherein the strain Streptomyces sp., strain 6982 (BCRC 910426). A method for producing a compound or a salt thereof, which is purified or isolated from a culture solution of a microorganism of the genus Streptomyces, which is represented by the formula (I). 13. The production method according to claim 12, wherein the Streptomyces sp. strain S. strain 6982 (BCRC 910426). A pharmaceutical composition comprising a compound of the first aspect of the patent application or a salt thereof, and a pharmaceutically acceptable excipient. A pharmaceutical composition for the prophylaxis or treatment of diabetes, which comprises the compound of the first aspect of the patent application or a salt thereof. 16. The use of a compound or a salt thereof as claimed in claim 1 for the manufacture of a pharmaceutical composition for the prevention or treatment of diabetes. 17. The use of a compound or a salt thereof as claimed in claim 1 for the prevention or treatment of diabetes. A method for preventing or treating diabetes, which comprises administering an effective amount of a compound of the first aspect of the patent application or a salt thereof to a patient for administration of φ.